Rational design of a "sense and treat" system to target amyloid aggregates related to Alzheimer's disease
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Xiaogang Qu(
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The aggregation of amyloid-β peptide (Aβ) is implicated in the pathology of Alzheimer's disease (AD), and Aβ oligomers are considered the most toxic species. Therefore, the detection and clearance of Aβ oligomers are crucial for the theranostic strategies for AD. However, effective methods for the detection of Aβ oligomers are rare, and only few of the oligomer-specific sensors have therapeutic functions as well. Recent studies have demonstrated that the toxicity of Aβ oligomers is related to the number of exposed hydrophobic residues. In this study, an oligomer-specific fluorescent probe, which was based on the hydrophobic regions that are exposed on Aβ oligomer surfaces was designed and synthesized. For improving the ability to recognize Aβ oligomers, the in situ treatment of AD symptoms and the ability to penetrate the blood-brain barrier, the probe and KLVFF peptide (an Aβ-target peptide) were modified on the surfaces of magnetic nanoparticles (MNP@NFP-pep). This complex could detect Aβ oligomers specifically, and achieve the wireless deep magnetothermally mediated disaggregation of Aβ aggregates with an alternating magnetic field. This work provides new insights into the development of a "sense and treat" system for AD therapy.
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Rational design of a "sense and treat" system to target amyloid aggregates related to Alzheimer's disease
), Xiaogang Qu(
)
Abstract
The aggregation of amyloid-β peptide (Aβ) is implicated in the pathology of Alzheimer's disease (AD), and Aβ oligomers are considered the most toxic species. Therefore, the detection and clearance of Aβ oligomers are crucial for the theranostic strategies for AD. However, effective methods for the detection of Aβ oligomers are rare, and only few of the oligomer-specific sensors have therapeutic functions as well. Recent studies have demonstrated that the toxicity of Aβ oligomers is related to the number of exposed hydrophobic residues. In this study, an oligomer-specific fluorescent probe, which was based on the hydrophobic regions that are exposed on Aβ oligomer surfaces was designed and synthesized. For improving the ability to recognize Aβ oligomers, the in situ treatment of AD symptoms and the ability to penetrate the blood-brain barrier, the probe and KLVFF peptide (an Aβ-target peptide) were modified on the surfaces of magnetic nanoparticles (MNP@NFP-pep). This complex could detect Aβ oligomers specifically, and achieve the wireless deep magnetothermally mediated disaggregation of Aβ aggregates with an alternating magnetic field. This work provides new insights into the development of a "sense and treat" system for AD therapy.
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Acknowledgements
Financial support was provided by the National Basic Research Program of China (973 Program) (No. 2012CB720602), the Project of Science and Technology Development Plan for Jilin Province (No. 20150520004JH) and the National Natural Science Foundation of China (NSFC) (Nos. 21210002, 21431007, 21402183 and 21533008).
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